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Immunity. 2013 Aug 22;39(2):298-310. doi: 10.1016/j.immuni.2013.07.019. Epub 2013 Aug 15.

Canonical Wnt signaling negatively modulates regulatory T cell function.

Author information

1
Department of Immunology, University Medical Center Utrecht, Utrecht 3584EA, The Netherlands.

Abstract

Foxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that T cell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active Wnt signaling disrupts Foxp3 transcriptional activity. A global chromatin immunoprecipitation sequencing comparison in Treg cells revealed considerable overlap between Foxp3 and Wnt target genes. The activation of Wnt signaling reduced Treg-mediated suppression both in vitro and in vivo, whereas disruption of Wnt signaling in Treg cells enhanced their suppressive capacity. The activation of effector T cells increased Wnt3a production, and Wnt3a levels were found to be greatly increased in mononuclear cells isolated from synovial fluid versus peripheral blood of arthritis patients. We propose a model in which Wnt produced under inflammatory conditions represses Treg cell function, allowing a productive immune response, but, if uncontrolled, could lead to the development of autoimmunity.

PMID:
23954131
DOI:
10.1016/j.immuni.2013.07.019
[Indexed for MEDLINE]
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